New Compound Protects Against Development of Liver
By Tim Parsons
School of Public Health
Scientists have identified a new compound called
CDDO-Im that protects against the development of liver
cancer in laboratory animals. Experiments led by
researchers at the Johns
Hopkins Bloomberg School of Public Health show CDDO-Im
to be effective at doses 100 times lower than other
compounds known to prevent cancer in people. Because of its
makeup, the researchers believe CDDO-Im could be
particularly effective in preventing cancers with a strong
link to inflammation, such as liver, colon, prostate and
gastric cancers. It could also play a role in preventing
diseases such as neurodegeneration, asthma and emphysema.
The findings are featured in the Feb. 15 issue of the
journal Cancer Research.
CDDO-Im is a synthetic compound that belongs to a
class of cancer-fighting compounds called triterpenoids
under development by Michael Sporn and other study
co-authors at Dartmouth Medical School. It is derived from
oleanolic acid, a naturally occurring substance found in
many plants. Other oleanolic derivatives are known to
reduce tumor growth in animals and humans.
Researchers believe CDDO-Im works by activating Nrf2,
a master switch known to direct certain enzymes to
stimulate the cell's defense mechanisms and remove harmful
chemicals from cells. "Activation of the Nrf2 pathway with
CDDO-Im could provide protection against a number of
diseases triggered by environmental agents," said lead
author Thomas Kensler, a professor with the Bloomberg
Department of Environmental Health Sciences.
In their research, Kensler and his colleagues treated
laboratory rats with varying doses of CDDO-Im. Two days
later, the rats were given aflatoxin, a naturally occurring
cancer-causing toxin. CDDO-Im treatment led to an 85
percent reduction in precancerous lesions at the lowest
dose of 50 micrograms per rat and a 99 percent reduction at
the highest dose of 5 milligrams.
Like other compounds derived from oleanolic acid,
CDDO-Im has strong anti-inflammatory properties, which the
researchers say makes it ideally suited to the prevention
of certain cancers. "When cells become inflamed, they can
produce reactive molecules, called free radicals, that can
damage DNA and promote cancer development," Kensler said.
"CDDO-Im can also inhibit cancer formation by interfering
with this inflammatory process."
Because it can stimulate the body's defense mechanisms
at such low doses, Kensler believes that CDDO-Im is an
excellent candidate for cancer prevention in humans. "If
this compound can produce such a potent and dramatic
reduction in the number of precancerous growths, it should
have an equally dramatic impact on the development of
actual cancers. This study suggests that we may be on the
right track in terms of chemoprevention. It may open the
door for a new class of compounds that could prevent a
number of diseases," Kensler said.
The National Institute of Environmental Health
Sciences and the National Cancer Institute, agencies of the
National Institutes of Health, provided funding to
researchers at the Bloomberg School for the study. Authors
are Melinda S. Yates, Mi-Kyoung Kwak, Patricia A. Egner,
John D. Groopman, Sridevi Bodreddigari, Thomas R. Sutter,
Karen J. Baumgartner, Bill D. Roebuck, Karen T. Liby, Mark
M. Yore, Tasdashi Honda, Gordon W. Gribble, Sporn and
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